Stroke, brought on by cerebrovascular disease, is a leading cause of death and permanent disability in the United States. The life threatening nature of the disease is motivation for the development of new diagnostic techniques to determine the prognosis of patients with cerebrovascular disease during the early hours after onset of symptoms, when reversible brain injury can be aided by acute interventions.
Diagnostic techniques presently being used, such as computed tomography scans, do not routinely detect brain damage until a few days after the onset of stroke. A better method is nuclear medicine imaging using radiolabeled amines which rapidly cross the normal blood brain barrier. Perfusion defects can be detected early using this technique since the scans mapping regional blood flow immediately display damage in patients who suffer strokes.
Two radioiodinated brain imaging amines that have been developed are N-isopropyl-p-iodoamphetamine (IMP) and N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-iodobenzyl)-1,3-propanediamine (HIPDM). IMP has shown an advantage over HIPDM of having almost twice the amount of activity in the brain five minutes after administration, leading to clearer images. It also clears the lungs faster resulting in better images since the scattering of high energy photons from the lung region is less. This minimizes the degradation of the brain image. These compounds are prepared by first synthesizing a halogenated precursor and then labeling by isotopic exchange. However, there are limitations to this synthetic approach. The specific activity is generally low due to presence of unlabeled starting material and the exchange reaction is slow and must be preformed at high temperatures. It is therefore necessary to provide compounds for efficient imaging of cerebral blood flow that are easy to make and result in clear images.